Evans Total Synthesis of — -FR

Returning to the work at hand, with the two building blocks merged together, 68 was advanced to 69 through a series of four separate synthetic operations, and then the complete 19-membered 

For a review on the Diels—Alder reaction in total synthesis, see K. C. Nicolaou, S. A. Snyder, T. Mon-tagnon, G. Vassilikogiannakis, Angew. Chem. 2002, 114, 1742 Angew. Chem. Int. Ed. 2002, 41, 1668. 

For a review on Diels—Alder reactions in the biosynthesis of natural products, see A. Ichihara, H. Oikawa in Comprehensive Natural Products Chemistry, VoL 5 (Eds. D. H. R. Barton, K. Nakanishi, O. Meth-Cohn), Elsevier, New York, 1999, pp. 367—408. For other examples in this book showing biomimetic Diels—Alder reactions, see Chapter 8 on manzamine A, Chapter 11 on the bisorbicillinoids, and Chapter 18 on vinblastine. 

For reviews and other examples of this general sequence, see a) L. F. Tietze, J. Bachmann, J. Wich-mann, Y. Zhou, T. Raschke, Liebigs Ann. 1997, 881 b) L. F. Tietze, Chem. Rev. 1996, 96, 115 c) L. F. Tietze, J. Bachmann, J. Wichmann, O. Burkhardt, Synthesis 1994, 1185. 

Macrocyclizations through Knoevenagel condensations are actually quite rare, and may only be limited to the formation of cyclic oligomers. For an example, see Y. Zhang, T. Wada, H. Sasabe, Chem. Commun. 

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